Devices for the automated release of liquid medicaments are normally used with patients who have a continuous and, in the course of the day, a varying need of a medicine which can be administered by subcutaneous infusion. Specific applications are, for example, certain pain therapies and the treatment of diabetes, in which computer controlled infusion pump devices, such as insulin pumps, are used. Such devices can be carried by a patient on the body, and can contain a certain amount of liquid medicament in a medicine reservoir in the form of a container. The medicine reservoir often comprises medicine sufficient for one or more days. The liquid medicament is supplied to the patient's body from the medicine reservoir through an infusion cannula or an injection needle.
Particularly in self-administration of medicaments, for example insulin, the patients that are using the medicament in question and administering it themselves by means of an infusion pump, are increasingly emphasizing convenience and discretion. As a consequence the dimensions of such infusion devices are limited, and in particular the overall length, width and thickness should be as small as possible, in order not be evident through clothing and to be carried comfortably as possible.
While there are fully or partly disposable single-use infusion pump devices, such devices are typically non-disposable and are loaded with a disposable drug cartridge. Disposable cartridges are preferable for sterility and contamination prevention reasons. They may be delivered either pre-filled with a certain liquid medicament, or empty, ready to be filled by a user. Said self-filling of containers has the advantage that also medicaments that are not readily available in pre-filled containers can be used for such infusion pump devices, thereby providing the patient with a larger choice of sources for his medicaments. Furthermore the stability of many medicaments in liquid form, particularly in plastic containers, can only be guaranteed by the manufacturer for a number of days.
The standard infusion pump devices that are carried on or near the body have a medicine reservoir with a cylindrical ampoule and a displacement piston, which is pushed into the ampoule by a piston rod or a threaded spindle in order to convey the liquid medicament. These known designs have the disadvantage of being longer and/or thicker than desired, with the resulting dimensions being detrimental to the provision of compact infusion pumps.
Manufacturers try to meet the demand of small infusion pump devices by various means. For example, the infusion pump can be divided into structural assemblies which are each arranged in their own, smaller, housings and can be joined to one another by wireless or wired connection. An example of such a modular infusion pump device is disclosed in US 2006/0184119 A1.
Another possibility is the use of containers of particularly flat construction. For example, a cylindrical ampoule may be replaced by a container with a rectangular or another suitable cross-section, and which interacts with a displacement piston of a corresponding shape. Different embodiments of such compact medicine reservoir devices are shown in WO 2008/122135 A1.
A further approach to reduce the overall volume of an infusion pump device is to replace the syringe-type dosing mechanism, in which a piston is displaced along a long container axis, by an actuator, thereby conveying the appropriate amount of liquid medicine by a downstream pump system. In such a device, a miniaturized pump is arranged downstream of the reservoir, and causes a suction pressure that conveys the product from the reservoir to its destination. An example for such a pump is WO 2004/009162 A1.
For some of such infusion pump devices, the suction pressure achievable with such a pump system is not very high. A suitable container for such devices is disclosed in US 2007/0123820 A1, comprising a flat container and a flat piston body arranged in the body in a sliding manner. When fully filled, such a container has a ratio between its maximum height and its overall width of less than 1.25. The cross-section area of the container in relation to the displacement axis is much larger than for conventional cylinder-piston arrangements, and already a comparably small pressure gradient as generated by a miniaturized pump is able to overcome the friction force of the piston sealing gliding on the inner container wall.
In another approach the rigid container and movable piston are replaced by a flexible container. Such a flexible container may, for example, have the form of two flexible wall sheets that are sealed together. Flexible containers have the advantage of a smaller volume surplus of the container in relation to its content, which reduces the manufacture costs and the achievable dimensions of an infusion pump device using such a flexible container. The volume of a flexible container for use in an infusion pump device may be up to 10 ml, for example. A typical range for diabetes therapy is 1.5 to 3.5 ml. For other therapies, e.g. pain therapies, which require other administration regimes, other volume ranges may be more preferable.
For use in an infusion pump device, the flexible container must be connected to a conduit system of the device. For that purpose, the flexible container may be provided with a port. Such a port can be mounted on the container with a flange sealed to a container wall sheet. US 2007/0049865 A1 discloses such a container. The port is provided with a septum, which is to be punctured by a hollow needle of the conduit system of the infusion pump device. Another possibility used for flexible containers are ports in the form of either flexible tubes or rigid connection pieces that are welded between the two sheets of the container at the periphery of the flexible container. The fastening of the port to the container, for example by gluing or welding, requires a precise production control to avoid high rejection rates, and which furthermore limits the choice of suitable materials.
A common problem of flexible containers with ports as used, for example, in IV bags, is the dead volume resulting between the collapsed container and the port. Said dead volume cannot be used, meaning that it cannot be emptied. Thus a complete drainage of the contents of a flexible container is not possible. The resulting loss of useable container volume due to the dead volume is particularly high for smaller containers, which are suitable for infusion pumps, with a total volume of only 5 ml or less. In standard liquid medicament containers for infusion pump devices, the dead volume may lie in the range of at least 5% of the overall volume. For single-use container filled with the medicament, the dead volume considerably increases the effective costs per dose and thus of the overall therapy costs, since a certain percentage of the medicament will inevitably remain in the container and has to be disposed. This cost effect is particularly important for expensive medicaments. In addition to the increased costs, the dead volume leads also to an increase of the overall volume of the flexible container, and thus of the infusion pump device with such a flexible container.
A further problem, particularly of flexible containers as they are known, is air remaining in the container. If, for example, a flexible container is provided empty, which is intended to be filled with the appropriate medicament by the user himself, the dead volume is initially filled with air. However, removing the air from flexible containers as they are known from the state of the art will require a certain skill of a user. If said air remains in the container or in the fluidic system of a pump system, air bubbles may be administered instead of the liquid medicament, which leads to potentially dangerous dosing errors. Furthermore, the administration of air into a patient's body should generally be avoided for medical reasons.
Yet another problem of air in the fluidic system is the reduced stiffness of the fluidic system. Due to the high compressibility of gases such as air in relation to liquids such as water, it becomes difficult to measure the exact pressure in the fluidic system. This impedes the detection of blockages or occlusions in the fluidic system of an infusion pump device by measuring the fluidic pressure.